Brands, Medical Use, Clinical Data
- Antitrichomonal Agents
- Pink film-coated oral tablets contain 500 mg or 250 mg of tinidazole.
Brands / Synonyms
Fasigyn; Tindamax; Tindamax
For the treatment of trichomoniasis caused by T. vaginalis in both female and male patients. Also for the treatment of giardiasis caused by G. duodenalis in both adults and pediatric patients older than three years of age and for the treatment of intestinal amebiasis and amebic liver abscess caused by E. histolytica in both adults and pediatric patients older than three years of age.
Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis, Giardia duodenalis (also termed G. lamblia), and Entamoeba histolytica. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.
Mechanism of Action
Tinidazole is an antiprotozoal agent. The nitro group of tinidazole is reduced by cell extracts of Trichomonas. The free nitro radical generated as a result of this reduction may be responsible for the antiprotozoal activity. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known.
Rapidly and completely absorbed under fasting conditions. Administration with food results in a delay in Tmax of approximately 2 hours and a decline in Cmax of approximately 10% and an AUC of 901.6 ± 126.5 mcg hr/mL.
There are no reported overdoses with tinidazole in humans. In acute studies with mice and rats, the LD 50 for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD 50 was > 2,000 mg/kg for both oral and intraperitoneal administration.
Biotrnasformation / Drug Metabolism
Hepatic, mainly via CYP3A4. Tinidazole, like metronidazole, is significantly metabolized in humans prior to excretion. Tinidazole is partly metabolized by oxidation, hydroxylation and conjugation. Tinidazole is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite.
Tindamax (tinidazole) is contraindicated in patients with hypersensitivity to tinidazole, any component of the tablet, or other nitroimidazole derivatives. Tindamax is contraindicated during the first trimester of pregnancy.
Although not studied specifically for tinidazole, the following drug interactions were reported for metronidazole,
a chemically-related nitroimidazole. Therefore, these drug interactions may occur with tinidazole.
Potential effect of tinidazole on other drugs
Warfarin and other oral coumarin anticoagulants. As with other nitroimidazole derivatives, tinidazole may
enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time.
This potential interaction should be considered when tinidazole is prescribed for patients on this type of
anticoagulant therapy. The dosage of oral anticoagulants may need to be adjusted during tinidazole co-administration
and up to 8 days after discontinuation.
Alcohols, Disulfiram. Alcoholic beverages and preparations containing ethanol or propylene glycol should be
avoided during tinidazole therapy and for three days afterward because abdominal cramps, nausea, vomiting, headaches
and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and
disulfiram concurrently. Though no similar reactions have been reported with tinidazole, tinidazole should not be
given to patients who have taken disulfiram within the last two weeks.
Lithium. Metronidazole has been reported to elevate serum lithium levels. It is not known if tinidazole
shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine
levels after several days of simultaneous lithium and tinidazole treatment to detect potential lithium
Phenytoin, Fosphenytoin. Fosphenytoin is a pro-drug of phenytoin. Concomitant administration of oral
metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the
clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally-administered
Cyclosporine, Tacrolimus. There are several case reports suggesting that metronidazole has the potential to
increase the levels of cyclosporine and tacrolimus. During tinidazole co-administration with either of these drugs,
the patient should be monitored for signs of calcineurin-inhibitor associated toxicities.
Fluorouracil. Metronidazole was shown to decrease the clearance of fluorouracil, resulting in an increase
in side-effects without an increase in therapeutic benefits. If the concomitant use of tinidazole and fluorouracil
cannot be avoided, the patient should be monitored for fluorouracil-associated toxicities.
Potential effect of other drugs on tinidazole
Simultaneous administration of tinidazole with drugs that induce liver microsomal enzymes (cytochrome P-450) such
as phenobarbital, rifampin, phenytoin and fosphenytoin (a pro-drug of phenytoin) may accelerate the
elimination of tinidazole, decreasing the plasma level of tinidazole. Simultaneous administration of drugs that
inhibit the activity of liver microsomal enzymes, such as cimetidine and ketoconazole, may prolong the
half-life and decrease the plasma clearance of tinidazole, increasing the plasma level of tinidazole.
Cholestyramine. Cholestyramine was shown to decrease the oral bioavailability of metronidazole by 21%.
Thus, it is advisable to separate dosing of cholestyramine and tinidazole to minimize any potential effect on the
oral bioavailability of tinidazole.
Oxytetracycline. Oxytetracycline was reported to antagonize the therapeutic effect of metronidazole.
Drug/Laboratory test interactions: Tinidazole, like metronidazole, may interfere with certain types of
determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase
(ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All
of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction
of nicotinamide adenine dinucleotide (NAD + [harr ] NADH). Potential interference is due to the similarity
of absorbance peaks of NADH and tinidazole.